Simulation of a trust and reputation based mitigation protocol for a black hole style attack on VANETs

From a security standpoint, VANETs (Vehicular ad hoc Networks) are vulnerable to attacks by malicious users, due to the decentralized and open nature of the wireless system. For many of these kinds of attacks detection is unfeasible, thus making it hard to produce security. Despite their characterization as dynamically reconfigurable networks, it is nonetheless essential to identify topology and population properties that can optimise mitigation protocols’ deployment. In this paper, we provide an algorithmic definition and simulation of a trust and mitigation based protocol to contain a Black Hole style attack on a VANET. We experimentally show its optimal working conditions: total connectivity, followed by a random network; connection to external networks; early deployment of the protocol and ranking of the message. We compare results with those of existing protocols and future work shall focus on repeated broadcasting, opportunistic message forwarding and testing on real data

Microcephaly and macrocephaly. A study on anthropometric and clinical data from 308 subjects

Head circumference is the auxological parameter that most correlates with developmental anomalies in childhood. Head circumference (HC) two standard deviations (SD) below or above the mean defines microcephaly and macrocephaly, respectively. The aim of this retrospective study was to explore anthropometric parameters and clinical characteristics among subjects with abnormalities in HC who had been referred for developmental assessment. One hundred and sixty four subjects with microcephaly and 144 subjects with macrocephaly were enrolled from birth to 18 months of age. Head circumference at birth and the association with variables related to maternal health status, gestational age, growth pattern, brain imaging and clinical characteristics were analyzed. In some cases, an etiological diagnosis was made. In the two considered conditions, we found different anthropometric and clinical associations, some of which were statistically significant, with implications for ongoing neurodevelopmental surveillance

Quinoline-based molecules targeting c-Met, EGF, and VEGF receptors and the proteins involved in related carcinogenic pathways

The quinoline ring system has long been known as a versatile nucleus in the design and synthesis of biologically active compounds. Currently, more than one hundred quinoline compounds have been approved in therapy as antimicrobial, local anaesthetic, antipsychotic, and anticancer drugs. In drug discovery, indeed, over the last few years, an increase in the publication of papers and patents about quinoline derivatives possessing antiproliferative properties has been observed. This trend can be justified by the versatility and accessibility of the quinoline scaffold, from which new derivatives can be easily designed and synthesized. Within the numerous quinoline small molecules developed as antiproliferative drugs, this review is focused on compounds effective on c-Met, VEGF (vascular endothelial growth factor), and EGF (epidermal growth factor) receptors, pivotal targets for the activation of important carcinogenic pathways (Ras/Raf/MEK and PI3K/AkT/mTOR). These signalling cascades are closely connected and regulate the survival processes in the cell, such as proliferation, apoptosis, differentiation, and angiogenesis. The antiproliferative biological data of remarkable quinoline compounds have been analysed, confirming the pivotal importance of this ring system in the efficacy of several approved drugs. Furthermore, in view of an SAR (structure-activity relationship) study, the most recurrent ligand–protein interactions of the reviewed molecules are summarized

Design and Manufacturing Issues in the Development of Lightweight Solution for a Vehicle Frontal Bumper

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Off-target-based design of selective hiv-1 protease inhibitors

The approval of the first HIV-1 protease inhibitors (HIV-1 PRIs) marked a fundamental step in the control of AIDS, and this class of agents still represents the mainstay therapy for this illness. Despite the undisputed benefits, the necessary lifelong treatment led to numerous severe side-effects (metabolic syndrome, hepatotoxicity, diabetes, etc.). The HIV-1 PRIs are capable of interacting with “secondary” targets (off-targets) characterized by different biological activities from that of HIV-1 protease. In this scenario, the in-silico techniques undoubtedly contributed to the design of new small molecules with well-fitting selectivity against the main target, analyzing possible undesirable interactions that are already in the early stages of the research process. The present work is focused on a new mixed-hierarchical, ligand-structure-based protocol, which is centered on an on/off-target approach, to identify the new selective inhibitors of HIV-1 PR. The use of the well-established, ligand-based tools available in the DRUDIT web platform, in combination with a conventional, structure-based molecular docking process, permitted to fast screen a large database of active molecules and to select a set of structure with optimal on/off-target profiles. Therefore, the method exposed herein, could represent a reliable help in the research of new selective targeted small molecules, permitting to design new agents without undesirable interactions

TTF-1/p63-positive poorly differentiated NSCLC: A histogenetic hypothesis from the basal reserve cell of the terminal respiratory unit

TTF-1 is expressed in the alveolar epithelium and in the basal cells of distal terminal bronchioles. It is considered the most sensitive and specific marker to define the adenocarcinoma arising from the terminal respiratory unit (TRU). TTF-1, CK7, CK5/6, p63 and p40 are useful for typifying the majority of non-small-cell lung cancers, with TTF and CK7 being typically expressed in adenocarcinomas and the latter three being expressed in squamous cell carcinoma. As tumors with coexpression of both TTF-1 and p63 in the same cells are rare, we describe different cases that coexpress them, suggesting a histogenetic hypothesis of their origin. We report 10 cases of poorly differentiated non-small-cell lung carcinoma (PD-NSCLC). Immunohistochemistry was performed by using TTF-1, p63, p40 (∆Np63), CK5/6 and CK7. EGFR and BRAF gene mutational analysis was performed by using real-time PCR. All the cases showed coexpression of p63 and TTF-1. Six of them showing CK7+ and CK5/6− immunostaining were diagnosed as “TTF-1+ p63+ adenocarcinoma”. The other cases of PD-NSCLC, despite the positivity for CK5/6, were diagnosed as “adenocarcinoma, solid variant”, in keeping with the presence of TTF-1 expression and p40 negativity. A “wild type” genotype of EGFR was evidenced in all cases. TTF1 stained positively the alveolar epithelium and the basal reserve cells of TRU, with the latter also being positive for p63. The coexpression of p63 and TTF-1 could suggest the origin from the basal reserve cells of TRU and represent the capability to differentiate towards different histogenetic lines. More aggressive clinical and morphological features could characterize these “basal-type tumors” like those in the better known “basal-like” cancer of the breast

Targeting SARS-CoV-2 Main Protease for Treatment of COVID-19: Covalent Inhibitors Structure-Activity Relationship Insights and Evolution Perspectives

The viral main protease is one of the most attractive targets among all key enzymes involved in the SARS-CoV-2 life cycle. Covalent inhibition of the cysteine145 of SARS-CoV-2 MPRO with selective antiviral drugs will arrest the replication process of the virus without affecting human catalytic pathways. In this Perspective, we analyzed the in silico, in vitro, and in vivo data of the most representative examples of covalent SARS-CoV-2 MPRO inhibitors reported in the literature to date. In particular, the studied molecules were classified into eight different categories according to their reactive electrophilic warheads, highlighting the differences between their reversible/irreversible mechanism of inhibition. Furthermore, the analyses of the most recurrent pharmacophoric moieties and stereochemistry of chiral carbons were reported. The analyses of noncovalent and covalent in silico protocols, provided in this Perspective, would be useful for the scientific community to discover new and more efficient covalent SARS-CoV-2 MPRO inhibitors

Fisurectomy and anoplasty with botulinum toxin injection in patients with chronic anal posterior fissure with hypertonia: a long-term evaluation

Chronic anal fissure\u2019s (CAF) etiopathogenesis remain unclear. CAF of the posterior commissure (CAPF) are often characterized by internal anal sphincter (IAS) hypertonia. The treatment of this disease aimed to reduce IAS hypertonia. Due to the high rate of anal incontinence after LIS, the employment of sphincter preserving surgical techniques associated to pharmacological sphincterotomy appears more sensible. The aim of our study is to evaluate the long-term results of fissurectomy and anoplasty with V\u2013Y cutaneous flap advancement associated to 30 UI of botulinum toxin injection for CAPF with IAS hypertonia. We enrolled 45 patients undergone to fissurectomy and anoplasty with V\u2013Y cutaneous flap advancement and 30 UI botulinum toxin injection. All patients were followed up for at least 5 years after the surgical procedure, with evaluation of anal continence, recurrence rate and MRP (Maximum resting pressure), MSP (Maximum restricting pressure), USWA (Ultrasound wave activity). All patients healed within 40 days after surgery. We observed 3 \u201cde novo\u201d post-operative anal incontinence cases, temporary and minor; the pre-operative ones have only temporary worsened after surgery. We reported 3 cases of recurrences, within 2 years from surgery, all healed after conservative medical therapy. At 5 year follow-up post-operative manometric findings were similar to those of healthy subjects. At 5 years after the surgical procedure, we achieved good results, and these evidences show that surgical section of the IAS is not at all necessary for the healing process of the CAPF